This proposal describes a well integrated program, involving eight independent investigators and their associates for the study of the microbicidal and tumoricidal properties of human mononuclear leukocytes. The eight specific projects that embody this proposal examine the differentiation of human mononuclear phagocytes from normal individuals and patients with cancer. The role(s) of lymphokines, produced by thymus dependent lymphocytes (T-cells), in the maturation, differentiation and activation of mononuclear phagocytes will be studied. We will characterize the effects of lymphokines, stimulated lymphocytes, antibodies, and bacterial adjuvants on the surface properties (I region gene products), receptors (Fc, complement, oligosaccharides), secretory products ((prostaglandins, leukotrienes, toxic oxygen products (H2O2, O2-, OH.)), microbicidal activities for the obligate intracellular parasite Trypanosoma cruzi, and/or the facultative intracellular pathogen Legionella pneumophila, and the tumoricidal activities against human melanoma and leukemia targets. The biochemical nature of the effector mechanisms used by human mononuclear leukocytes to destroy microbial pathogens and tumor cells will be identified, and the ways parasites, bacteria and tumor cells resist killing will be examined. Efforts will be made to use the nude mouse an an "in vivo" model of tumoricidal effector activities of activated human mononuclear phagocytes against human tumor cells. An integral part of the overall program is the identification and characterization of the human equivalent of the dendritic cells. In the mouse, dendritic cells are potent stimulators of the allogeneic and syngeneic mixed leukocyte reaction and the formation of cytotoxic T-cells. Identification and isolation of a human equivalent of this cell should help to clarify the roles of human T-cells in lymphokine production, mononuclear phagocyte differentiation, and generation of helper suppressor and cytotoxic cells. Most of the studies propposed in this program call for the use of monoclonal antibodies to isolate and/or characterize the cells and molecules involved. Studies are also proposed requiring separation of mononuclear cells by centrifugal elutriation. For these reasons, a core laboratory for mononuclear antibody production and cell separation form a integral part of this program.